The purpose of this study is to estimate the maximum tolerated doses (MTD) of CRLX101 when administered in combination with weekly paclitaxel in women with recurrent or persistent, epithelial ovarian, fallopian tube or primary peritoneal cancer. Determine through pharmacokinetic evaluation(sometimes described as what the body does to a drug, refers to the movement of drug into, through and out of the body-the time and course of its absorption, bioavailability, distribution, metabolism, and excretion) whether or not the disposition of paclitaxel is affected by the concurrent administration of CRLX101.
Recurrent ovarian cancer represents a therapeutic challenge. Patients with resistant disease, showing progression within six months of platinum-containing therapy, have a poor prognosis, with median overall survival (OS) approximately 12 months.Ultimately most patients with recurrent disease ultimately develop platinum resistance, and novel strategies are needed. In this setting the most active agents are pegylated liposomal doxorubicin (PLD), paclitaxel and topotecan. Multiple trials have demonstrated that combination therapy produces increased toxicity without improved efficacy. This study proposes to examine the combination of CRLX101 in combination with weekly paclitaxel. Preclinical studies show synergistic activity in the SKOV3 human ovarian cancer xenograft ovarian cancer cell lines (14), as well as in vivo (15,16), perhaps via an antiangiogenic mechanism.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
30
Massachusetts General Hospital
Boston, Massachusetts, United States
Washington University
St Louis, Missouri, United States
The Ohio State University
Columbus, Ohio, United States
University of Oklahoma / Stephenson Cancer Center
Oklahoma City, Oklahoma, United States
Thomas Jefferson University
Philadelphia, Pennsylvania, United States
Women & Infants Hospital of Rhode Island
Providence, Rhode Island, United States
University of Virginia Health System
Charlottesville, Virginia, United States
1. To estimate the maximum tolerated doses (MTD) of CRLX101 when administered in combination with weekly paclitaxel in women with recurrent or persistent, epithelial ovarian, fallopian tube or primary peritoneal cancer.
The highest dose with \<2 patients with DLTs out of 6 DLT-evaluable patients
Time frame: 6 months
Comparison of pharmacokinetic perimeters including max concentration (Cmax), time to maximum concentration (Tmax), AUC, elimination half-life for CRLX101 and paclitaxel
PK
Time frame: 6 months
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